Biology subjects

Fontaine, E.

Publications and source records attributed to Fontaine, E..

3 recordsLinked to original sources

bioRxiv2026

Cfap410a and Cby work together with tissue-specific requirements to build Drosophila ciliary transition zones

Cilia and flagella perform essential physiological functions in eukaryotes, and defects in these organelles cause several human diseases, including cancer and ciliopathies. The architecture of cilia is highly organized. The ciliary compartment is separated from the cytoplasm by the transition zone (TZ). The severity of ciliopathies linked to TZ assembly defects highlights the TZ's critical role. Although several core conserved complexes are involved in TZ assembly, variations in TZ composition are associated with structurally and functionally diverse cilia. Here, we identify Cfap410a as a novel component of the ciliary TZ in the two Drosophila ciliated tissues, male germ cells and sensory neurons. Cfap410a is one of the two Drosophila paralogs (Cfap410a and Cfap410b) of human CFAP410, whose mutations are associated with axial spondylo-metaphyseal dysplasia, retinitis pigmentosa and amyotrophic lateral sclerosis. We show here that Cfap410a is a proximity partner of Cby and that they act cooperatively in the hierarchy of the TZ assembly program by bridging the CEP290 and MKS transition zone modules. Simultaneous loss of Cfap410a and Cby halts ciliary growth by disrupting TZ formation in multiple types of Drosophila ciliated cells, each of which exhibiting varying dependence on these two proteins. Interestingly, the function of Cfap410a and Cfap410b are not functionally redundant, indicating that the two proteins have evolved towards specific functions. In summary, our results propose a novel role for CFAP410a at the TZ and provide an explanation for how deregulation of conserved TZ components could lead to tissue-specific ciliopathies.

cell biology↗

bioRxiv2024

Spatial self-organization of cancer stem cell niches revealed by live single-cell imaging

Phenotypic plasticity is a major factor of tumor heterogeneity and treatment resistance. In particular, cancer stem cells (CSCs) represent a small subpopulation within tumors with self-renewal and tumor-forming capabilities. Understanding reprogramming, maintenance, and lineage properties of CSCs requires dedicated tools to disentangle the respective influences of phenotypic inheritance and cell-cell interactions. Here we set up ultra-wide field microscopy of breast cancer cell lines expressing a stemness fluorescent reporter for several days. The fluorescent reporter distinguishes three phenotypes: cancer stem cells (CSCs), cancer differentiated cells (CDCs) and intermediate/transiting cancer cells (iCCs). Spatial statistics indicate significant zonation, aka phenotypic niches, with CSC clustering near each other but away from CDCs. Surprisingly, single cell time series reveal spontaneous reprogramming events from CDC to CSC even in unperturbed populations. We identify that such transitions are prone to arise during the cell cycle. Moreover, lineage analysis shows that the phenotype is partially inherited from ancestor cells. However, such heredity is not sufficient to explain the spatial properties of the cell population, which also depend on cell-cell interactions. Indeed, we identified that phenotypic transitions of cancer cells are influenced by the phenotypic state of neighboring cells. Reprogramming into CSCs is respectively promoted and inhibited by the presence of CSCs and CDCs in the neighborhood. Altogether, our results disentangle how phenotypic inheritance and intercellular interactions orchestrate the spatio-temporal self-organization of cancer cell heterogeneity, maintaining a subpopulation of CSCs within niches.

systems biology↗

bioRxiv2021

Comparative therapeutic strategies for preventing aortic rupture in a mouse model of vascular Ehlers Danlos syndrome

We created a knock-in Col3a1+/G182R mouse model with spontaneous mortality caused by thoracic aortic rupture that recapitulates a rare vascular genetic disease of type III collagen, the vascular Ehlers-Danlos syndrome (vEDS). Investigation of this model showed lower survival rate in males caused by aortic rupture, thin non-inflammatory arteries and altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of Col3a1+/G182R mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vEDS.

genetics↗